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Item Corticotropin-releasing factor system in the lateral septum: Implications in the pathophysiology of obesity(2022-09-20) Olivares-Barraza, Rossy; Marcos, José Luis; Martínez-Pinto, Jonathan; Fuenzalida, Marco; Bravo, Javier A.; Gysling, Katia; Sotomayor-Zárate, RamónObesity is a pandemic associated with lifestyles changes. These include excess intake of obesogenic foods and decreased physical activity. Brain areas, like the lateral hypothalamus (LH), ventral tegmental area (VTA), and nucleus accumbens (NAcc) have been linked in both homeostatic and hedonic control of feeding in experimental models of diet-induced obesity. Interestingly, these control systems are regulated by the lateral septum (LS), a relay of γ-aminobutyric (GABA) acid neurons (GABAergic neurons) that inhibit the LH and GABAergic interneurons of the VTA. Furthermore, the LS has a diverse receptor population for neurotransmitters and neuropeptides such as dopamine, glutamate, GABA and corticotropin-releasing factor (CRF), among others. Particularly, CRF a key player in the stress response, has been related to the development of overweight and obesity. Moreover, evidence shows that LS neurons neurophysiologically regulate reward and stress, although there is little evidence of LS taking part in homeostatic and hedonic feeding. In this review, we discuss the evidence that supports the role of LS and CRF on feeding, and how alterations in this system contribute to weight gain obesity.Item Corticotropin-releasing factor system in the lateral septum: Implications in the pathophysiology of obesity(2022-09-20) Olivares-Barraza, Rossy; Marcos, José Luis; Martínez-Pinto, Jonathan; Fuenzalida, Marco; Bravo, Javier A.; Gysling, Katia; Sotomayor-Zárate, RamónObesity is a pandemic associated with lifestyles changes. These include excess intake of obesogenic foods and decreased physical activity. Brain areas, like the lateral hypothalamus (LH), ventral tegmental area (VTA), and nucleus accumbens (NAcc) have been linked in both homeostatic and hedonic control of feeding in experimental models of diet-induced obesity. Interestingly, these control systems are regulated by the lateral septum (LS), a relay of γ-aminobutyric (GABA) acid neurons (GABAergic neurons) that inhibit the LH and GABAergic interneurons of the VTA. Furthermore, the LS has a diverse receptor population for neurotransmitters and neuropeptides such as dopamine, glutamate, GABA and corticotropin-releasing factor (CRF), among others. Particularly, CRF a key player in the stress response, has been related to the development of overweight and obesity. Moreover, evidence shows that LS neurons neurophysiologically regulate reward and stress, although there is little evidence of LS taking part in homeostatic and hedonic feeding. In this review, we discuss the evidence that supports the role of LS and CRF on feeding, and how alterations in this system contribute to weight gain obesity.Item Farmacoterapia de la Obesidad: definiendo una nueva enfermedad(2021) Castillo, Rodrigo L.; Chávez, Diego; Olivares-Barraza, Rossy; Saldias, Cristina; Sánchez-Lombardi, Ignacio; Marcos, José L.; Cruz, Gonzalo; Sotomayor-Zárate, RamónPara un alto porcentaje de pacientes que no logran controlar su peso con solo cambiar sus hábitos de alimentación y ejercicio, es necesario tener medicamentos que apoyen los cambios en el estilo de vida. Desafortunadamente, la historia y la evolución de la farmacoterapia para el tratamiento de la obesidad ha estado llena de dilemas relacionados con la seguridad, la eficacia, el abuso y los efectos adversos. Actualmente, los criterios de la FDA y la EMA para la aprobación de un medicamento son muy estrictos, como sucedió en 2010 y principios de 2011 cuando se rechazaron las cuatro opciones farmacéuticas. Existen múltiples dianas terapéuticas en estudio, quizás una de las más interesantes sea la inhibición de la hormona Grelina y el aporte de la grasa visceral y su proceso termogénico. Las pocas alternativas terapéuticas actuales llevan a los pacientes a intentar ayudar con suplementos para adelgazar, muchos de ellos ineficaces. En este contexto, la determinación de nuevas dianas moleculares más selectivas y la progresión de modelos preclínicos son la gran paradoja por resolver. Esta revisión se centra en la farmacología clínica de los fármacos más frecuentes contra la obesidad, algunas novedades en ensayos clínicos y paradigma futuro sobre regulación, control y pérdida de peso significativa.Item Obesogenic Diet-Induced Neuroinflammation: A Pathological Link between Hedonic and Homeostatic Control of Food Intake(2023-01-11) Marcos, José Luis; Olivares-Barraza, Rossy; Ceballo, Karina; Wastavino, Melisa; Ortiz, Víctor; Riquelme, Julio; Martínez-Pinto, Jonathan; Muñoz, Pablo; Cruz, Gonzalo; Sotomayor-Zárate, RamónObesity-induced neuroinflammation is a chronic aseptic central nervous system inflammation that presents systemic characteristics associated with increased pro-inflammatory cytokines such as interleukin 1 beta (IL-1β) and interleukin 18 (IL-18) and the presence of microglia and reactive astrogliosis as well as the activation of the NLRP3 inflammasome. The obesity pandemic is associated with lifestyle changes, including an excessive intake of obesogenic foods and decreased physical activity. Brain areas such as the lateral hypothalamus (LH), lateral septum (LS), ventral tegmental area (VTA), and nucleus accumbens (NAcc) have been implicated in the homeostatic and hedonic control of feeding in experimental models of diet-induced obesity. In this context, a chronic lipid intake triggers neuroinflammation in several brain regions such as the hypothalamus, hippocampus, and amygdala. This review aims to present the background defining the significant impact of neuroinflammation and how this, when induced by an obesogenic diet, can affect feeding control, triggering metabolic and neurological alterations.Item Obesogenic Diet-Induced Neuroinflammation: A Pathological Link between Hedonic and Homeostatic Control of Food Intake(2023-01-11) Marcos, José Luis; Olivares-Barraza, Rossy; Ceballo, Karina; Wastavino, Melisa; Ortiz, Víctor; Riquelme, Julio; Martínez-Pinto, Jonathan; Muñoz, Pablo; Cruz, Gonzalo; Sotomayor-Zárate, RamónObesity-induced neuroinflammation is a chronic aseptic central nervous system inflammation that presents systemic characteristics associated with increased pro-inflammatory cytokines such as interleukin 1 beta (IL-1β) and interleukin 18 (IL-18) and the presence of microglia and reactive astrogliosis as well as the activation of the NLRP3 inflammasome. The obesity pandemic is associated with lifestyle changes, including an excessive intake of obesogenic foods and decreased physical activity. Brain areas such as the lateral hypothalamus (LH), lateral septum (LS), ventral tegmental area (VTA), and nucleus accumbens (NAcc) have been implicated in the homeostatic and hedonic control of feeding in experimental models of diet-induced obesity. In this context, a chronic lipid intake triggers neuroinflammation in several brain regions such as the hypothalamus, hippocampus, and amygdala. This review aims to present the background defining the significant impact of neuroinflammation and how this, when induced by an obesogenic diet, can affect feeding control, triggering metabolic and neurological alterations.